The increased VLDL and decreased HDL commonly associated with non-insulin dependent diabetes are of concern because of their possible role in the etiology of the greatly increased cardiovascular disease in this disorder. Moreover, it has not been established how therapy of diabetes, with either diet or oral hypoglycemic agents, influences lipoprotein metabolism. This study compares VLDL and LDL metabolism, fatty acid metabolism, and lipoprotein lipase activities in type II diabetics and in age and weight-matched non-diabetics. Studies were also conducted in diabetics before and after therapy with sulfonylureas and also diabetics are being compared on high and low fat diets. The data suggest that diabetics have abnormal VLDL and that diabetes influences VLDL-TG production independent of that of apoB, possibly through elevations of free-fatty acids or glucose. LDL concentrations in diabetics are influenced by two opposing changes - increase in direct removal of VLDL, but decrease in FCR for VLDL. Improvement of glycemic control is followed by significant falls in VLDL-TG and LDL cholesterol and reversal of abnormalities of HDL subfractions and VLDL composition. Transfer to a high carbohydrate, low saturated fat diet leads to decreases in LDL and no change in HDL. This was accompanied by no change in VLDL in most diabetics; two brothers, however, showed significant increases in VLDL and glucose, indicating that diabetics must be carefully monitored when transferred to high carbohydrate regimens.